Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites

Evert, BJ; Chen, S; McConville, R; Steel, RWJ; Healer, J; Boddey, JA; Huntimer, L; Rehm, BHA

Author(s): Evert, BJ; Chen, S; McConville, R; Steel, RWJ; Healer, J; Boddey, JA; Huntimer, L; Rehm, BHA;
Details: Publication Year 2021-11-29,Volume 6,Issue #1,Page 141
Journal Title: NPJ vaccines
Abstract: The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria. Here we developed a particulate malaria vaccine based on the same CSP epitopes but using biopolymer particles (BPs) as an antigen carrier system. Specific B- and T-cell epitope-coated BPs were assembled in vivo inside an engineered endotoxin-free mutant of Escherichia coli. A high-yield production process leading to ~27% BP vaccine weight over biomass was established. The epitope-coated BPs were purified and their composition, i.e., the polymer core and epitope identity, was confirmed. Epitope-coated BPs were used alongside soluble peptide epitopes and empty BPs to vaccinate sheep. Epitope-coated BPs showed enhanced immunogenicity by inducing anti-NANP antibody titre of EC50 > 150,000 that were at least 20 times higher than induced by the soluble peptides. We concluded that the additional T-cell epitope was not required as it did not enhance immunogenicity when compared with the B-cell epitope-coated BPs. Antibodies specifically bound to the surface of Plasmodium falciparum sporozoites and efficiently inhibited sporozoite motility and traversal of human hepatocytes. This study demonstrated the utility of biologically self-assembled epitope-coated BPs as an epitope carrier for inclusion in next-generation malaria vaccines.
Publisher: NPG
Research Division(s): Infectious Diseases And Immune Defence; Population Health And Immunity
PubMed ID: 34845267
Publisher's Version: https://doi.org/10.1038/s41541-021-00408-2
Open Access at Publisher's Site: https://doi.org/10.1038/s41541-021-00408-2
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: EvertBJ et al_npj Vaccines_2021.pdf - (1.73MB, application/pdf)

Creation Date: 2021-12-07 12:03:58

Last Modified: 2021-12-07 12:17:59